Sputum metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio correlates with airflow obstruction in asthma and chronic bronchitis

Asthma and chronic bronchitis are inflammatory diseases with extracellular matrix (ECM) remodeling and collagen deposition. Collagen homeostasis is controlled by metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). We evaluated MMP and TIMP balance in induced sputum of 10 control, 31 untreated asthmatic, and 16 chronic bronchitic subjects. We first performed zymographic analysis to identify the profile of MMPs. Zymography revealed a similar MMPs profile in all populations studied and that MMP-9 was the major enzyme released. We then measured, using enzyme immunoassay, the concentrations of MMP-9 and of its inhibitor TIMP-1 and evaluated whether airflow limitation m…

Similar cellular composition of induced sputum in Marathon and Half-Marathon runners

In our previous studies, we reported increased neutrophil (PMN) differential counts in induced sputum of marathon (M) runners (Bonsignore et al, 2001). Conversely, increased bronchial epithelial cell (BEC) differential counts were found in half-marathon (HM) runners (Chimenti et al, 2010). To better understand the differences previously found between M and HM runners, we studied 11 non-asthmatic amateur athletes (HM n=6, M n=5, age: 44.5±6.7 yrs, race time: HM 101±18 min, M 218±35 min) participating to the 2012 Palermo Marathon. We collected induced sputum samples 4 to 5 days before the race (PRE), 2 hours after the race (RACE), and the following morning (POST). Induced sputum was processed…

Airway cell composition at rest and after an all-out test in competitive rowers

Med Sci Sports Exerc. 2004 Oct;36(10):1723-9. Airway cell composition at rest and after an all-out test in competitive rowers. Morici G, Bonsignore MR, Zangla D, Riccobono L, Profita M, Bonanno A, Paternò A, Di Giorgi R, Mirabella F, Chimenti L, Benigno A, Vignola AM, Bellia V, Amato G, Bonsignore G. SourceDepartment of Experimental Medicine Italian National Research Council (CNR), Palermo, Italy. Abstract PURPOSES: This study was designed to assess: a) whether rowing affects airway cell composition, and b) the possible relationship between the degree of ventilation during exercise and airway cells. SUBJECTS AND METHODS: In nine young, nonasthmatic competitive rowers (mean age +/- SD: 16.2 …

Increased airway inflammatory cells in endurance athletes: what do they mean?

Background Inflammatory cells are increased in the airways of end urance athletes, but their role in causing exercise-induced respiratory symptoms and bronchoconstriction, or their possible long-term consequences, are uncertain. Aim To put the results of athlete studies in perspective, by analysing the pathogenesis of airway cell changes and their impact on respiratory function. Results Athletes of different endurance sports at rest showed increased airway neutrophils. Elite swimmers and skiers also showed large increases in airway eosinophils and lymphocytes, possibly related to chronic, exercise-related exposure to irritants or cold and dry air, respectively. Post-exercise studies reporte…

Effect of cilomilast (Ariflo) on TNF-α, IL-8, and GM-CSF release by airway cells of patients with COPD

Background: Inflammation in chronic obstructive pulmonary disease (COPD) is characterised by increased neutrophilic infiltration of the airways. Cilomilast, a novel selective phosphodiesterase 4 inhibitor in clinical development for COPD treatment, exerts anti-inflammatory effects. The ability of cilomilast to inhibit the release of neutrophil chemoattractants such as tumour necrosis factor (TNF)-α, interleukin (IL)-8, and granulocyte-macrophage colony stimulating factor (GM-CSF) by bronchial epithelial cells and sputum cells isolated from 10 patients with COPD, 14 normal controls, and 10 smokers was investigated. Methods: Bronchial epithelial cells obtained by bronchial brushing and sputum…

Chronic obstructive pulmonary disease and neutrophil infiltration: role of cigarette smoke and cyclooxygenase products.

Cigarette smoke is the main cause of chronic obstructive pulmonary disease (COPD), where it can contribute to the observed airway inflammation. PGE(2) is produced within human airways, and both pro- and anti-inflammatory activities have been reported. We quantitated PGE(2) concentrations in induced sputum supernatants from different groups of subjects and correlated the obtained values to neutrophil infiltration as well as to the expression of cyclooxygenase-2 (COX-2). Cigarette smoke extract (CSE) was used to evaluate the effect of smoking on COX-2 and PGE(2) receptor expression as well as on PGE(2) release in neutrophils and alveolar macrophages (AM) obtained from normal donors. The effec…

Airway inflammation in nonasthmatic amateur runners

Elite athletes show a high prevalence of symptoms and signs of asthma, but no study has assessed the acute effects of endurance exercise on airway cells in nonasthmatic athletes. We measured exhaled nitric oxide (NO) and collected samples of induced sputum after 3% NaCl aerosol administration for 20 min in nonasthmatic middle-aged amateur runners after the Fourth Palermo International Marathon and 6–9 wk later (habitual training period) at baseline. After the marathon, exhaled NO ( n = 9 subjects) was higher [27 ± 9 parts/billion (ppb)] than at baseline (12 ± 4 ppb; P < 0.0005). Polymorphonuclear neutrophil (PMN) counts in induced sputum were much higher in runners (91.2 ± 3.6% of total…

Increased prostaglandin E2 concentrations and cyclooxygenase-2 expression in asthmatic subjects with sputum eosinophilia.

Abstract Background Prostaglandin E 2 (PGE 2 ) is known to be produced within human airways, but it is not clear whether in airway diseases it can play a deleterious or a beneficial role. Recently it has been reported that PGE 2 can enhance eosinophil survival in vitro. Objective To evaluate whether the concentrations of PGE 2 in asthmatic airways correlate with the number of eosinophils and can be responsible for eosinophil-enhanced survival and to identify the cyclooxygenase isoform contributing to the synthesis of PGE 2 by cells present in asthmatic airways. Methods Reversed-phase high-performance liquid chromatography and/or specific radioimmunoassay was used to measure PGE 2 concentrat…

Acetylcholine leads to signal transducer and activator of transcription 1 (STAT-1) mediated oxidative/nitrosative stress in human bronchial epithelial cell line

AbstractThe induction of nitric oxide synthase (iNOS) expression via the signal transducer and activator of transcription 1 (STAT-1) is involved in the mechanism of oxidative/nitrosative stress. We investigated whether acetylcholine (ACh) generates oxidative/nitrosative stress in bronchial epithelial cells during airway inflammation of COPD and evaluated the effects of Tiotropium, a once-daily antimuscarinic drug, and Olodaterol, a long-acting β2-agonist on these mechanisms. Human bronchial epithelial cells (16-HBE) were stimulated (4h, 37°C) with induced sputum supernatants (ISSs) from healthy controls (HC) (n=10), healthy smokers (HS) (n=10) or COPD patients (n=10), as well as with ACh (f…

Reticulocytes in untreated obstructive sleep apnoea.

Background and Aim. The short, repetitive hypoxaemic episodes observed in obstructive sleep apnoea (OSA) may determine small augmentations in mature red blood cells. It is unknown whether they affect reticulocyte release. This study explored whether the number and degree of maturation of circulating reticulocytes may be altered in OSA, possibly through the effect of erythropoietin. Methods. Fifty male adult patients with suspected OSA, normoxic during wakefulness, were studied. After nocturnal polysomnography, a blood sample was withdrawn for blood cells count, erythropoietin, iron and transferrin determination. Reticulocyte concentration and degree of immaturity [high (H), medium (M), or l…

Increased Levels of Elastase and α1-Antitrypsin in Sputum of Asthmatic Patients

Asthma and chronic bronchitis are inflammatory diseases associated with remodeling of the extracellular matrix (ECM). Elastin, a major component of the ECM in the airways, has been previously found to be disrupted in asthma and chronic bronchitis. This study was aimed at evaluating whether elastin disruption might be associated with an imbalance between elastase (active and total) and alpha1-proteinase inhibitor (alpha1-PI), the main inhibitor of elastase. We measured elastase and alpha1-PI in induced sputum obtained from 16 control subjects, 10 healthy smokers, 19 asthmatic patients, and 10 chronic bronchitis patients. We also assessed the possible origin of elastase, evaluating its levels…

Effect of age and asthma duration upon elastase and alpha1-antitrypsin levels in adult asthmatics

In asthmatic subjects an imbalance between elastase and alpha1-antitrypsin (alpha1-PI) exists. This study aims to evaluate whether ageing per se affects the levels of elastase. Both young and elderly asthmatics with comparable severity and duration of disease, as well as young and elderly healthy subjects, underwent an induced sputum procedure to measure levels of elastase and alpha1-PI. The percentage of sputum neutrophils and eosinophils was higher in young and elderly asthmatics than in young and elderly controls. The levels of both total and active elastase were significantly higher in young and elderly asthmatics than in young and elderly controls, and directly correlated with the perc…

Novel Perspectives in the Detection of Oral and Nasal Oxidative Stress and Inflammation in Pediatric United Airway Diseases

United airway disease (UAD) concept proposed that asthma and rhinitis are both different clinical manifestation of a single inflammatory process. The aim of this study is to assess in upper and lower airways the level of inflammation and oxidative stress and to investigate the relationship between biomarkers in persistent allergic rhinitis (PER) and in concomitant asthma with PER. By a crosssectional study we measured oral and nasal (FENO) and oral and nasal EBC 8-isoprostane, LTB4 and PGE2 in children with PER (n=14) and with PER and concomitant intermittent asthma (IA; n=25), mild persistent asthma (mA; n=28), moderate persistent asthma (MA; n=13) and in Healthy Controls (HCs; n=13). Oral…

Effect of nebulized beclomethasone on airway inflammation and clinical status of children with allergic asthma and rhinitis: a randomized, double-blind, placebo-controlled study.

We aimed to evaluate the therapeutic effect of nebulized beclomethasone dipropionate (nBDP) on both allergic asthma and rhinitis. In a randomized, double-blind, placebo-controlled study, 40 children (mean age 10.7 ± 2.1 years) with allergic asthma and rhinitis received either nBDP (daily dose of 800 µg, administered twice daily) or placebo for 4 weeks (with a face mask), after a 2-week run-in period of clinical assessment. Nasal and oral fractional exhaled nitric oxide (FeNO) measurements together with pulmonary function tests, nasal and oral exhaled breath condensate (EBC) collection for pH and interleukin-5 (IL-5) measurements as well as nasal and bronchial symptom scores were obtained at…

Advances in asthma pathophysiology: stepping forward from the Maurizio Vignola experience

Maurizio Vignola was a superb and innovative researcher, who wrote seminal papers on the biology of airway epithelium in asthma. Inflammation and remodelling were the main topics of his research, mostly conducted in biopsy specimens from patients with asthma of variable severity, encompassing the entire spectrum of the disease from mild to severe asthma. His observations contributed to define the biology of asthma as we know it today, and opened the way to the personalised treatment of asthma. His group has successfully continued to investigate the biology and clinical aspects of bronchial asthma, with major interest in the clinical use of biomarkers to monitor disease activity, and in the …

Nebulized Beclomethasone In The Treatment Of Childhood Mild Intermittent Asthma With Seasonal Allergic Rhinitis. A Randomized, Double-Blind, Placebo-Controlled Study

β2 long-acting and anticholinergic drugs control TGF-β1-mediated neutrophilic inflammation in COPD

AbstractWe quantified TGF-β1 and acetylcholine (ACh) concentrations in induced sputum supernatants (ISSs) from 18 healthy controls (HC), 22 healthy smokers (HS) and 21 COPDs. ISSs from HC, HS and COPD as well as rhTGF-β1 were also tested in neutrophil adhesion and in mAChR2, mAChR3 and ChAT expression experiments in human bronchial epithelial cells (16-HBE). Finally, we evaluated the effects of Olodaterol (a novel inhaled β2-adrenoceptor agonist) and Tiotropium Spiriva®, alone or in combination, on neutrophil adhesion and mAChRs and ChAT expression in stimulated 16-HBE. The results showed that 1) TGF-β1 and ACh concentrations are increased in ISSs from COPD in comparison to HC and HS, and T…

Increased levels of Th17 cells are associated with non-neuronal acetylcholine in COPD patients.

T-lymphocytes, including Th17-cells and T-cells expressing acetylcholine (ACh), are key components of systemic inflammation in chronic obstructive pulmonary disease (COPD). We investigated whether ACh promotes Th17 cells in COPD. ACh, IL-17A, IL-22, RORγt, FOXP3 expression and AChIL-17A, AChIL-22, AChRORγt coexpression was evaluated in peripheral blood mononuclear cells (PBMC) from COPD patients (n=16), healthy smokers (HS) (n=12) and healthy control subjects (HC) (n=13) (cultured for 48 h with PMA) by flow cytometry. Furthermore, we studied the effect of Tiotropium (Spiriva®) (100 nM) and Olodaterol (1nM) alone or in combination, and of hemicholinium-3 (50 μM) on AChIL-17A, AChIL-22, AChRO…

Acetylcholine mediates the release of IL-8 in human bronchial epithelial cells by a NFkB/ERK-dependent mechanism

Acetylcholine may play a role in cell activation and airway inflammation. We evaluated the levels of both mRNA and protein of muscarinic M(1), M(2), M(3) receptors in human bronchial epithelial cell line (16HBE). 16HBE cells were also stimulated with acetylcholine and extracellular signal-regulated kinase1/2 (ERK1/2) and NFkB pathway activation as well as the IL-8 release was assessed in the presence or absence of the inhibitor of Protein-kinase (PKC) (GF109203X), of the inhibitor of mitogenic activated protein-kinase kinase (MAPKK) (PDO9805), of the inhibitor of kinaseB-alpha phosphorilation (pIkBalpha) (BAY11-7082), and of muscarinic receptor antagonists tiotropium bromide, 4-Diphenylacet…

15-Lipoxygenase expression and 15(S)-hydroxyeicoisatetraenoic acid release and reincorporation in induced sputum of asthmatic subjects

Recent evidence shows that 15(S)-hydroxy-eicoisatetraenoic acid (15[S]-HETE) can be released and rapidly reincorporated into cellular lipids. These mechanisms exert several immunoregulatory functions that may be relevant in airway inflammation.Our purpose was to evaluate the levels of both soluble and cell-associated 15(S)-HETE and to examine 15-lipoxygenase (15-LO) messenger RNA (mRNA) expression in sputum samples obtained from 10 control and 18 asthmatic subjects.Levels of 15(S)-HETE were measured by reverse-phase HPLC separation followed by RIA in supernatants and in cell membrane-extracted phospholipids after acid hydrolysis. 15-LO mRNA was evaluated by primed in situ hybridization (PRI…

Noninvasive methods for the detection of upper and lower airway inflammation in atopic children

Background Exhaled nitric oxide (FE NO ) and exhaled breath condensate (EBC) are noninvasive methods to assess inflammation. Objective To investigate the role of the FE NO and of the EBC pH and IL-5 levels in atopic children. Methods We evaluated oral and nasal FE NO and the pH and IL-5 of oral and nasal EBC in children with atopic dermatitis (AD; n=18), allergic rhinitis (AR; n=18), intermittent asthma (n = 21), moderate persistent asthma (n = 18), and healthy controls (HCs; n=16). Results Oral FE NO was significantly increased in asthma, whereas the nasal values were increased in AR and asthma in comparison with HCs. The pH of oral EBC was lower in AD and asthma than in AR and HCs, wherea…

Increased leptin/leptin receptor pathway affects systemic and airway inflammation in COPD former smokers

Andreina Bruno1, Marinella Alessi2, Simona Soresi2, Anna Bonanno1, Loredana Riccobono1, Angela Marina Montalbano1, Giusy Daniela Albano1, Mark Gjomarkaj1, Mirella Profita11Institute of Biomedicine and Molecular Immunology, Italian National Research Council, Palermo, Italy; 2Dipartimento Biomedico di Biomedicina Interna e Specialistica, University Palermo, ItalyBackground: Leptin, a hormone produced mainly by adipose tissue, regulates food intake and energy expenditure. It is involved in inflammatory diseases such as chronic obstructive pulmonary disease (COPD) and its deficiency is associated with increased susceptibility to the infection. The leptin receptor is expressed in the lung and in…

In vitro effects of flunisolide on MMP-9, TIMP-1, fibronectin, TGF-beta1 release and apoptosis in sputum cells freshly isolated from mild to moderate asthmatics

Corticosteroids play an important role in inflammation and remodelling of airways and are considered an important therapeutic target in asthma. Inflammation in asthma is characterized by a dysregulation of eosinophil apoptosis and of markers of airways remodelling. We evaluated the ability of flunisolide to inhibit in vitro the release of metalloproteinases-9 (MMP-9), tissue inhibitor metalloproteinases-1 (TIMP-1), transforming growth factor (TGF-beta) and fibronectin by sputum cells (SC) as well as to induce sputum eosinophil apoptosis.The SC, isolated from induced sputum samples of 12 mild-to-moderate asthmatics, were cultured for 24 h in the presence or absence of flunisolide (1, 10 and …

IL-17A induces chromatin remodeling promoting IL-8 release in bronchial epithelial cells: Effect of Tiotropium

Abstract Aims IL-17A plays a key role in the persistence of airway inflammation, oxidative stress, and reduction of steroid-sensitivity in COPD. We studied the effect of IL-17A on chromatin remodeling and IL-8 production. Main methods We measured the levels of IL-8 and IL-17A in induced sputum supernatants (ISS) from healthy controls (HCs), healthy smokers (HSs), and COPD patients by enzyme-linked immunosorbent assay (ELISA). A human bronchial epithelial cell line (16HBE) was stimulated with ISS from HCs, HSs, or COPD subjects. IL-8 was evaluated in 16HBE by Western blot and real-time polymerase chain reaction (PCR). Histone deacetylase 2 (HDAC2), acetyl histone H3 (Ac-His H3) (k9) and inhi…

Th17 immunity in children with allergic asthma and rhinitis: a pharmacological approach

Th17 cells and IL-17A play a role in the development and progression of allergic diseases. We analyzed the IL-17A levels in sputum supernatants (Ss), nasal wash (NW) and plasma (P) from Healthy Controls (HC) and children with Asthma/Rhinitis. We tested the expression of IL-17A, RORγ(t) and FOXP3 in peripheral blood T-lymphocytes from intermittent and mild-moderate asthma. The effect of Budesonide and Formoterol was tested "in vitro" on IL-17A, RORγ(t) and FOXP3 expression in cultured T-lymphocytes from mild-moderate asthma/persistent rhinitis patients, and on nasal and bronchial epithelial cells stimulated with NW and Ss from mild-moderate asthma/persistent rhinitis. Further, the effect of …

Airway cells after swimming outdoors or in the sea in nonasthmatic athletes

BONSIGNORE, M. R., G. MORICI, L. RICCOBONO, M. PROFITA, A. BONANNO, A. PATERNO, R. DI GIORGI, L. CHIMENTI, P. ABATE, F. MIRABELLA, A. M. VIGNOLA, and G. BONSIGNORE. Airway Cells after Swimming Outdoors or in the Sea in Nonasthmatic Athletes. Med. Sci. Sports Exerc., Vol. 35, No. 7, pp. 1146–1152, 2003. Marathon runners and elite swimmers showed increased inflammatory cells in the airways at baseline. Although airway neutrophils increase further after a marathon race, the airway response to swimming is unknown. The aim of this study was to assess the effects of swimming on airway cells. To avoid the concomitant effects of chronic exposure to chlorine, the study was conducted in seven nonasth…

The Role of Transforming Growth Factor-β1 in Airway Inflammation of Childhood Asthma

TGF-beta-targeting structural and inflammatory cells has been implicated in the mechanisms leading to the inflammatory and restructuring processes in asthma, suggesting an impact of TGF-beta1 signaling on the development and persistency of this disease. We investigated the potential early involvement of TGF-beta1 activity in the immunological and molecular mechanisms underlying progression of inflammation in childhood asthma. We evaluated the levels of TGF-beta1 in induced sputum supernatants (ISSs) and the expression of small mother cell against decapentaplegic (Smad) 2 and Smad7 proteins in induced sputum cells (ISCs) from children with intermittent asthma (IA), moderate asthma (MA) and c…

Is the acidity of ascitic fluid a reliable index in making the presumptive diagnosis of spontaneous bacterial peritonitis?

Ascitic fluid pH and arterial-ascitic fluid pH gradient were compared to ascitic fluid polymorphonuclear cell count in 84 patients with cirrhotic ascites and in 12 with malignant ascites to assess their role as diagnostic tests for spontaneous bacterial peritonitis and to clarify the relationship between ascitic fluid pH and lactate. Ascitic fluid pH was significantly lower (pH 7.30) in spontaneous bacterial peritonitis (n = 18) and probable spontaneous bacterial peritonitis (n = 12) than in sterileascites (pH 7.41; n = 54). Since blood pH levels were not different in the presence of infection, arterial-ascitic fluid pH gradient was significantly higher in spontaneous bacterial peritonitis …

Relaxin in Obstructive Sleep Apnea: Relationship with Blood Pressure and Inflammatory Mediators

<b><i>Background:</i></b> Obstructive sleep apnea (OSA) is associated with nocturnal intermittent hypoxia, which may be responsible for increased circulating levels of vascular endothelial growth factor (VEGF) and inflammatory mediators, such as metalloproteinases (MMPs), and which contributes to the pathogenesis of systemic hypertension. Why some OSA patients remain normotensive is poorly understood. Relaxin-2, a pregnancy hormone, may sometimes circulate in men and could increase in hypoxic conditions. It exerts a vasodilatory activity and can modulate the release of molecules, such as MMPs and VEGF. <b><i>Objectives:</i></b> The objective o…

Muscarinic receptors, leukotriene B4 production and neutrophilic inflammation in COPD patients.

Background:  Acetylcholine (ACh) plays an important role in smooth muscle contraction and in the development of airway narrowing; preliminary evidences led us to hypothesize that ACh might also play a role in the development of airways inflammation in chronic obstructive pulmonary disease (COPD). Methods:  We evaluated the concentrations of leukotriene B4 (LTB4) in induced sputum, and the expression of Ach M1, M2, and M3 receptors in sputum cells (SC) obtained from 16 patients with COPD, 11 smokers, and 14 control subjects. The SC were also treated with ACh and the production of LTB4 assessed in the presence or absence of a muscarinic antagonist (oxitropium). In blood monocytes, we evaluate…

IL-17A-associated IKK-α signaling induced TSLP production in epithelial cells of COPD patients.

Thymic stromal lymphopoietin (TSLP) is a cytokine expressed in the epithelium, involved in the pathogenesis of chronic disease. IL-17A regulates airway inflammation, oxidative stress, and reduction of steroid sensitivity in chronic obstructive pulmonary disease (COPD). TSLP and IL-17A were measured in induced sputum supernatants (ISs) from healthy controls (HC), healthy smokers (HS), and COPD patients by enzyme-linked immunosorbent assay. Human bronchial epithelial cell line (16HBE) and normal bronchial epithelial cells were stimulated with rhIL-17A or ISs from COPD patients to evaluate TSLP protein and mRNA expression. The effects of the depletion of IL-17A in ISs, an anticholinergic drug,…

In vitro anticholinergic drugs affect CD8+ peripheral blood T-cells apoptosis in COPD

Novel pharmacological strategies are aimed at the resolution of systemic inflammation in COPD potentiating peripheral blood T-cell (PBT-cell) apoptosis. Although muscarinic acetylcholine receptors (mAChRs) M(3) and choline-acetyltransferase (ChAT) participate in the airway inflammation of COPD, their role in PBT-cell apoptosis remains unexplained. We evaluated in PBT-cells from COPD patients, smoker (S) and control (C) subjects: (1) apoptosis (by annexin V binding), (2) mAChR M(3) and ChAT expression, acetylcholine (ACh)-binding; (3) choline levels in serum and PBT-cells extracts. We tested the effects of Tiotropium (Spiriva(®)) and hemicholinium-3 (HCh-3) on apoptosis, NFκB pathway, caspas…

Blood pressure changes after automatic and fixed CPAP in obstructive sleep apnea. Relationship with nocturnal sympathetic activity.

Treatment of obstructive sleep apnea (OSA) by continuous positive airway pressure (CPAP) usually causes a reduction in blood pressure (BP), but several factors may interfere with its effects. In addition, although a high sympathetic activity is considered a major contributor to increased BP in OSA, a relationship between changes in BP and in sympathetic nervous system activity after OSA treatment is uncertain. This study was undertaken to assess if, in OSA subjects under no pharmacologic treatment, treatment by CPAP applied at variable levels by an automatic device (APAP) may be followed by a BP reduction, and if that treatment is associated with parallel changes in BP and catecholamine exc…

25-Hydroxyvitamin D, IL-31, and IL-33 in Children with Allergic Disease of the Airways

Low vitamin D is involved in allergic asthma and rhinitis. IL-31 and IL-33 correlate with Th2-associated cytokines in allergic disease. We investigated whether low vitamin D is linked with circulating IL-31 and IL-33 in children with allergic disease of the airways. 25-Hydroxyvitamin D [25(OH) Vit D], IL-31, and IL-33 plasma levels were measured in 28 controls (HC), 11 allergic rhinitis (AR) patients, and 35 allergic asthma with rhinitis (AAR) patients. We found significant lower levels of 25(OH) Vit D in AR and in AAR than in HC. IL-31 and IL-33 plasma levels significantly increased in AAR than HC. IL-31 and IL-33 positively correlated in AR and AAR. 25(OH) Vit D deficient AAR had higher l…

Cigarette smoke alters the EZH2/DAB2IP expression in bronchial epithelial cells. A risk factor for lung cancer in COPD patients

Cigarette smoke is an environmental risk factor for COPD and Lung cancer, leading causes of morbidity and mortality worldwide. In cancer, enhancer of zeste homolog 2 (EZH2) silenced disabled homolog 2 interacting protein gene (DAB2IP) (tumor-suppressor gene) bytri-methylation of lysine 27 on histone H3 (H3K27me3). We studied EZH2 and DAB2IP expression in airway epithelial cells from COPD patients and their potential involvement in the progression of COPD toward lung cancer. We assessed EZH2 and DAB2IPimmunoreactivity in bronchial epithelial cells from surgical specimens of COPD patients and healthy control subjects (HC) by immunohistochemistry. Bronchial epithelial cell line (16HBE), primar…

15(S)-HETE modulates LTB(4) production and neutrophil chemotaxis in chronic bronchitis.

We evaluated the levels of 15(S)-hydroxyeicosatetraenoic acid [15(S)-HETE] and the expression of 15-lipoxygenase (15-LO) mRNA in induced sputum obtained from 10 control and 15 chronic bronchitis subjects. 15(S)-HETE was evaluated by reverse phase high-performance liquid chromatography separation followed by specific RIA. 15-LO mRNA expression was determined by primed in situ labeling. The levels of both soluble and cell-associated 15(S)-HETE resulted significantly higher in chronic bronchitis than in control subjects. The percentage of cells expressing 15-LO mRNA was significantly higher in chronic bronchitis than in control subjects ( P < 0.01). Double staining for specific cell type ma…

Beclomethasone dipropionate and formoterol reduce oxidative/nitrosative stress generated by cigarette smoke extracts and IL-17A in human bronchial epithelial cells.

Interleukin-17A (IL-17A), cigarette smoke and oxidative/nitrosative stress are involved in inflammatory airway diseases, and the mechanisms behind these processes are still poorly understood. We investigated whether recombinant human IL-17A (rhIL-17A), in combination with cigarette smoke extracts (CSE), increases the levels of inducibile nitric oxide synthase (iNOS), reactive oxygen species, nitrotyrosine (NT) and the activation of signal transducer and activator of transcription 1 (STAT-1) in normal human bronchial epithelial cells (16HBE). The effect of beclomethasone dipropionate (BDP), formoterol and their combination was also evaluated. We demonstrated that rhIL-17A or CSE alone increa…

Bronchial epithelial damage after a half-marathon in nonasthmatic amateur runners.

Am J Physiol Lung Cell Mol Physiol. 2010 Jun;298(6):L857-62. Epub 2010 Apr 2. Bronchial epithelial damage after a half-marathon in nonasthmatic amateur runners. Chimenti L, Morici G, Paternò A, Santagata R, Bonanno A, Profita M, Riccobono L, Bellia V, Bonsignore MR. SourceDept. Biomedico Di Medicina Interna & Specialistica, Section of Pneumology, Univ. of Palermo, Via Trabucco 180, 90146 Palermo, Italy. laurachimenti@yahoo.it Abstract High neutrophil counts in induced sputum have been found in nonasthmatic amateur runners at rest and after a marathon, but the pathogenesis of airway neutrophilia in athletes is still poorly understood. Bronchial epithelial damage may occur during intense exer…

Cigarette smoke alters non-neuronal cholinergic system components inducing MUC5AC production in the H292 cell line.

Abstract Cigarette smoke extract (CSE) affects the expression of Choline Acetyl-Transferase (ChAT), muscarinic acetylcholine receptors, and mucin production in bronchial epithelial cells. Mucin 5AC (MUC5AC), muscarinic acetylcholine receptor M3, ChAT expression, acetylcholine levels and acetylcholine binding were measured in a human pulmonary mucoepidermoid carcinoma cell line (H292) stimulated with CSE. We performed ChAT/RNA interference experiments in H292 cells stimulated with CSE to study the role of ChAT/acetylcholine in MUC5AC production. The effects of Hemicholinium-3 (HCh-3) (50 μM) (a potent and selective choline uptake blocker) and Tiotropium bromide (Spiriva ® ) (100 nM), alone o…